Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The synapse is a shotgun

15.07.2005


New model challenges textbook definition



Researchers have constructed a new detailed map of the three-dimensional terrain of a synapse -- the junction between neurons which are critical for communication in the brain and nervous system. The "nano-map," which shows the tiny spines and valleys resolved at nanometer scale, or one-billionth of a meter, has already proven its worth in changing scientists’ views of the synaptic landscape.

Using the map as a guide, the research team, led by Howard Hughes Medical Institute investigator Terrence Sejnowski, has developed a biologically accurate computer simulation of synaptic function. The simulation combines 3-D electron microscope maps with computer simulation and physiological measurements from real neurons. Their in silico modeling indicates that the synapse may behave more like a shotgun than a rifle when it comes to firing the neurotransmitters involved in neuronal communication.


The textbook view of the synapse describes it as a place where rifle-like volleys of neurotransmitter are launched from one defined region of the sending neuron to another defined target on the receiving neuron. In contrast, the new data suggest that synapse can act like a shotgun, firing buckshot-like bursts of neurotransmitter to reach receptors arrayed beyond the known receiving sites. The researchers say that right now they have little idea of how the synaptic shotgun functions.

The research was published in the July 15, 2005, issue of the journal Science. Sejnowski, who is at The Salk Institute, and colleagues Darwin Berg and Mark Ellisman, both of the University of California, San Diego, led the research team, which also included co-authors from Carnegie Mellon University and the University of Pittsburgh.

In the collaborative studies, Ellisman and his colleagues first used electron microscopic tomography -- the microscopist’s equivalent of a CAT scan -- to create a detailed 3-D map of the synapse of a chick ciliary ganglion. This ganglion is a cluster of neurons that connect the brain to the iris of the eye. It launches the neurotransmitter acetylcholine from sac-like vesicles across the synapse to two types of receptors, called alpha 7 and alpha 3.

Sejnowski and his colleagues transformed their map into a functional computer model by incorporating the physiological details of neurotransmitter release sites and receptors. The researchers then compared the behavior of the model under different scenarios with the electrophysiological behavior of actual ganglia measured in Berg’s laboratory.

The results, said Sejnowski, provide evidence for a different concept of the synapse. "The image of this ganglion is not one of a simple synapse with a single release site, but multiple release sites. And it shows alpha 3 receptors within the postsynaptic region, but alpha 7 receptors outside this region. Our model showed that if we assumed that neurotransmitter is released only from vesicles in active zones, where everybody thinks it is released, we get a very bad match to actual properties of the neuron. But if we model broader neurotransmitter release, where these alpha 7 receptors are located, we can match the actual properties of the synapse very accurately." This type of broader neurotransmitter distribution is called ectopic release.

"We can only be sure of data on this one type of neuron, the ciliary ganglion," said Sejnowski. "But we are confident that this evidence points to ectopic release, and this means that you can’t really trust the traditional textbook view -- in which all the vesicles are released at the active zone -- that’s taken for granted now."

The function of shotgun neurotransmitter release is unknown, said Sejnowski. "There’s just nothing solid on our radar screen right now," he said. "There is speculation that ectopic release represents some sort of spillover that neurons use under certain circumstances. Or, it may be an alternative mode of neurotransmission that neurons use at different points in their life cycle." Sejnowski and his colleagues have initiated further studies using their simulation technique to confirm the ectopic release mechanism and explore its possible functions.

"Although we are convinced that ectopic release exists, any time you question an accepted concept, there will be doubt and resistance," said Sejnowski. "So, we will continue to develop this new picture of the synapse to convince doubters, because this is such a different way of looking at how the synapse functions." Sejnowski said that he and his collaborators will extend their study to other types of synapses that are more complex and difficult to study.

More broadly, said Sejnowski, the new 3-D modeling technique could offer a powerful tool for understanding neurological disease, such as myasthenia gravis, a common disorder in which a defect in nerve impulse transmission results in muscle weakness. In this and other neurological diseases, "there may be an anomaly at the receptor level, but it is impossible to pinpoint the problem with existing techniques. With our modeling technique, we can explore the detailed geometry of the damaged tissue and ask how much of that anomaly is caused by the geometry itself," he said.

"Once we have pinned down where the real problem is, we can use the model as a fantastic tool for drug discovery. We can tell drug developers precisely where the anomaly is and where they should focus drug discovery efforts."

Jim Keeley | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>